A reduction in the high incidence and mortality of colorectal (CR) cancer in the United States by early discovery and removal of CR cancers and premalignant adenomas may be achieved by intensively screening asymptomatic people who are at high risk for CR cancer. One of two large populations thought to be in this high risk category are people with a past history of any CR adenoma or cancer; colonoscopy is being widely recommended for screening all such people. A second group for whom colonoscopy has been recommended are those with a strong family history of CR cancer (not including polyposis or cancer family syndromes). Implementation of such recommendations would be extremely costly and would overwhelm existing skilled personnel. Furthermore, adequate, unbiased data from prospective studies of first-time colonoscopy in asymptomatic people is not yet available. Therefore, it is not possible to accurately predict the various degrees of increased risk conferred by the wide range of past and family histories encountered in clinical practice. The benefit of colonoscopy in these groups has not been demonstrated. We propose to establish new guidelines for screening with colonoscopy by continuing to conduct and analyze findings from our pilot colonoscopy screening program begun in 1980. By 1986 our goal is to have performed first-time colonoscopy on at least 750 asymptomatic members of the Kaiser Foundation Health Plan who meet eitheir of the above high risk criteria. We will analyze the relationship between their carefully documented risk factors (e.g. characteristics and number of past neoplasms, number and relationship of relatives with CR cancer, age) and specific findings on colonoscopy. This will provide a unique opportunity to observe wide differences in risk within these large populations and to identify subgroups at high enough risk to justify the costs and risks of colonoscopy. Preliminary analysis of our first 229 colonoscopies indicates that different types and degrees of risk can be identified and correlated with colonoscopy findings. This supports our belief that the completed study will define small subgroups of these large populations for whom screening with colonoscopy will be appropriate. Our final guidelines may then recommend that the majority of these people be screened with less costly and invasive methods, resulting in a vast reduction in the potential cost of screening for colon cancer nationwide.